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Defective CD95/APO-1/Fas signal complex formation in the human autoimmune lymphoproliferative syndrome, type Ia.

Authors: Martin, D A  Zheng, L  Siegel, R M  Huang, B  Fisher, G H  Wang, J  Jackson, C E  Puck, J M  Dale, J  Straus, S E  Peter, M E  Krammer, P H  Fesik, S  Lenardo, M J 
Citation: Martin DA, etal., Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4552-7.
Pubmed: (View Article at PubMed) PMID:10200300

Heterozygous mutations in the CD95 (APO-1/Fas) receptor occur in most individuals with autoimmune lymphoproliferative syndrome (ALPS) and dominantly interfere with apoptosis by an unknown mechanism. We show that local or global alterations in the structure of the cytoplasmic death domain from nine independent ALPS CD95 death-domain mutations result in a failure to bind the FADD/MORT1 signaling protein. Despite heterozygosity for the abnormal allele, lymphocytes from ALPS patients showed markedly decreased FADD association and a loss of caspase recruitment and activation after CD95 crosslinking. These data suggest that intracytoplasmic CD95 mutations in ALPS impair apoptosis chiefly by disrupting death-domain interactions with the signaling protein FADD/MORT1.


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RGD Object Information
RGD ID: 12904015
Created: 2017-05-15
Species: All species
Last Modified: 2017-05-15
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.